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科学家建立新冠病毒非转基因小鼠感染模型

本期文章:《细胞》:Online/在线发表

2020年6月10日,《细胞》杂志在线发表了美国华盛顿大学医学院Michael S. Diamond课题组的最新成果。他们研发了小鼠新冠病毒(SARS-CoV-2)感染模型,并证明了中和抗体的保护作用。

研究人员通过鼻内给药将编码人类血管紧张素转换酶2(hACE2)的复制缺陷型腺病毒转导到BALB/c小鼠中,并在肺组织中建立了受体表达。hACE2转导的小鼠被SARS-CoV-2高效感染,这导致肺部病毒滴度高、肺部病理和体重减轻。中和性单克隆抗体的给药移减少了肺部的病毒负担,减轻了炎症和体重丢失。SARS-CoV-2感染和发病的小鼠模型开发将加快治疗剂和疫苗的测试和部署。

SARS-CoV-2引起了数百万人感染的大流行。评估抑制SARS-CoV-2感染和治疗疾病的潜在疗法和疫苗的局限性之一是缺乏大量易感小型动物。由于其ACE2受体的种属特异性差异,因此市售的小鼠实验室品系不容易被SARS-CoV-2感染。

附:英文原文

Title: A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies

Author: Ahmed O. Hassan, James Brett Case, Emma S. Winkler, Larissa Thackray, Natasha M. Kafai, Adam L. Bailey, Broc T. McCune, Julie M. Fox, Rita E. Chen, Wafaa B. Al Soussi, Jackson S. Turner, Aaron J. Schmitz, Tingting Lei, Swathi Shrihari, Shamus P. Keeler, Daved H. Fremont, Suellen Greco, Paul B. McCray, Stanley Perlman, Michael J. Holtzman, Ali H. Ellebedy, Michael S. Diamond

Issue&Volume: 2020-06-10

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.

DOI: 10.1016/j.cell.2020.06.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30742-X

期刊信息

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216

官方网址:https://www.cell.com/

投稿链接:https://www.editorialmanager.com/cell/default.aspx

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